BEIRUT — Al-Qaeda formally dissociated itself from its onetime affiliate in Iraq and Syria on Monday, culminating months of feuding and exposing the dwindling influence of the group’s leadership over an emerging new generation of radicals.

The repudiation of the Islamic State of Iraq and Syria came after the failure of repeated effortsby al-Qaeda leader Ayman al-Zawahiri to heal a dispute between ISIS and the officially anointed al-Qaeda affiliate Jabhat al-Nusra that has erupted in fighting in parts of rebel-held northern Syria.

ISIS “is not a branch of the al-Qaeda group . . . does not have an organizational relationship with it and [al-Qaeda] is not the group responsible for their actions,” al-Qaeda’s General Command said in a statement, marking the first time the leadership has formally repudiated an affiliate.

The rejection means that al-Qaeda no longer has representation in Iraq, where ISIS originated and where it has rebounded in recent months from the setbacks inflicted by U.S. troops to pose a significant challenge to Prime Minister Nouri al-Maliki’s control over the country.

It also leaves Jabhat al-Nusra, which is widely regarded among Syrians as more moderate than the hard-line ISIS, as the sole representative of al-Qaeda in Syria, where a multitude of armed groups are battling to overthrow Syrian President Bashar al-Assad and also, in some places, one another.

A U.S. counterterrorism official called the al-Qaeda announcement “unprecedented” and said Zawahiri had been left with “little choice but to announce a rupture that, for all intents and purposes, had already taken place.” But despite the weight the al-Qaeda brand still carries among jihadists worldwide, the official said, ISIS “has never been dependent on AQ core for resources or direction, so the tangible impact of the decision may not be that significant.” The official was not authorized to discuss the matter on the record.

In a briefing for reporters Monday, State Department spokeswoman Jen Psaki said that no policy changes were anticipated in response to the al-Qaeda move. “The fact to remember here is that both ISIS and al-Nusra are designated terrorist organizations,” she said. “Yes, they’ve been fighting each other for months, but that doesn’t change our view of both of those groups.”

The al-Qaeda statement suggested that the notorious intractability of ISIS, the most extreme of the Islamist groups fighting in Syria, was to blame for the break. It cited the importance of “consultation” and “teamwork,” qualities that ISIS has ignored in its aggressive expansion across northern Syria since it announced its formation last April.

“Clearly, Zawahiri believes that ISIS is a liability to the al-Qaeda brand,” said Aaron Zelin, who tracks jihadist movements at the Washington Institute for Near East Policy. “They are not playing nice with other groups and they are acting as a sovereign state, aggravating other rebels and hurting the effort against the regime.”

The group’s brutal tactics, including beheadings, floggings and bans on smoking, music and other perceived un-Islamic behaviors, have incurred the wrath of many ordinary Syrians, culminating a month ago in a widespread revolt against ISIS across northern Syria in which the al-Qaeda-affiliated Jabhat al-Nusra has fought ISIS alongside more moderate rebels.

But ISIS has fought back and has succeeded in retaining the northeastern province of Raqqah and significant portions of rural Aleppo, along with many of the area’s resources — including oil fields — that help it to operate independently of the al-Qaeda leadership.

Although Jabhat al-Nusra now is the sole al-Qaeda affiliate in Syria, ISIS is the group that is more aggressively pursuing the al-Qaeda agenda of establishing an Islamist caliphate by setting up the institutions of state that enable it to administer the areas it controls, said Aymenn al-Tamimi, who monitors jihadist activity in Iraq and Syria with the Middle East Forum.

“Al-Qaeda central doesn’t control territory in the manner ISIS does,” he said.

Jabhat al-Nusra’s fighters have greater reach across Syria, however, and participate in battles throughout the country in alliance with more moderate groups. U.S. officials cite the group as a long-term threat to American interests far more often than ISIS, and though it has not overtly threatened the United States, Director of National Intelligence James R. Clapper Jr. told a Senate hearing last week that Jabhat al-Nusra “does have aspirations for attacks on the homeland.”

The dispute points to the new complexities of the jihadist movement, which has spawned multiple new groups across the region in the wake of the Arab Spring uprisings, Zelin said.

“You have this wide tapestry of jihadi groups now, like a spider’s web,” he said. “All of these groups have the same ideology, they’re part of the jihadi framework, but they might have different focuses.”

It is too early to tell, however, whether the split will herald a wider regional rupture or is simply the consequence of the long friction between Zawahiri and ISIS’s Iraqi leader Abu Bakr al-Baghdadi. Much will depend on how other al-Qaeda-linked groups in the region respond, said Bruce Riedel, director of the Brookings Institution’s Intelligence Project.

“The al-Qaeda core brand still has a lot of attraction, maybe not in Iraq but in a lot of other places,” he said. “The game of terrorism is not a popularity contest . . . and Zawahiri has a legitimacy that Baghdadi doesn’t have.”

However, he added, “al-Qaeda in Iraq has flown the coop.”

Brian Fishman, a counterterrorism research fellow with the New America Foundation in Washington who has written extensively on al-Qaeda and its affiliates, said that Zawahiri’s action reflects an internal debate that dates to the founding of al-Qaeda in Iraq in 2006 and friction between the group’s then-leader, Abu Musab al-Zarqawi, and Osama bin Laden.

The “lesson” for al-Qaeda of Zarqawi, who was known for his brutality and who was killed by U.S. forces in Iraq in 2006, Fishman said, “is Zawahiri and al-Qaeda central essentially recognizing that not all press is good press. That’s something bin Laden understood.”

Also on Monday, 26 people were killed in and around rebel-held areas of the northern city of Aleppo in the Syrian government’s ongoing barrel bombing campaign, in which warplanes drop barrels on residential areas, usually causing devastation across a wide area.